AB1256 WORTH’S DISEASE (LRP5 HIGH-BONE-MASS): CASE REPORT AND REVIEW OF THE LITERATURE
Authors: G. De Mattia, M. Maffi, M. Mosca, M. Mazzantini
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Worth's disease is a rare autosomal dominant sclerosing bone dysplasia determining high bone mass. It is caused by mutations of the <i>low-density lipoprotein receptor-related protein 5 (LRP5</i>) gene. Clinical findings include torus palatinus and craniofacial changes, such as increased gonial angle [1]. The absence of neurological involvement has long been considered a key aspect to discriminate between Worth's disease and Van Buchem's disease, in which cranial nerve deficits and intracranial hypertension are frequent [2]. Alternative names have been employed to describe Worth's disease, such as "autosomal dominant osteosclerosis", "Van Buchem's disease, type 2", and "LRP5 high-bone-mass (HBM)". The rarity of the disorder, the use of several denominations and the lack of reviews have rendered research of information on Worth's disease complicated and confusing. <h3>Objectives</h3> To gather all case reports of Worth's disease and provide comprehensive data on the condition, and to describe a patient with neurological involvement. <h3>Methods</h3> After collecting all case reports, we assessed the prevalence of neurological involvement and other relevant clinical and laboratory findings. A thorough clinical, radiological, and genetic assessment was performed on an affected patient. <h3>Results</h3> A 44-year-old Caucasian woman was referred to us in 2009 for chronic and debilitating dorsolumbar pain (Visual Analogue Scale 8/10). Since her twenties, she has been affected by chronic and disabling low back pain, frontoparietal headache, hypo-/anosmia, and numbness and tingling of arms, face, and oral cavity. She noticed the early appearance of facial changes that became more evident with time. In 1999, external hearing aids were placed due to complete mixed hearing loss caused by the narrowing of internal and external acoustic meati. At presentation, clinical examination revealed prominent jaw, frontal bossing, and torus palatinus. She denied previous bone fractures. Family history was unremarkable. A complete skeletal survey revealed endosteal hyperostosis of the limbs and severe osteosclerosis of clavicles, ribs, vertebrae, hip, and cranium, in the absence of deformities except for a deepened and widened jaw. Bone scintigraphy with technetium-99m was normal. Dual-energy X-ray absorptiometry (<i>DEXA</i>) scan revealed T-score +10.8 (Z-score +11.1) and bone mineral density (BMD) of 2.5 g/cm<sup>2</sup> for L1-L4 spine, T-score +6.5 (Z-score +6.2) and BMD of 1.8 g/cm<sup>2</sup> for femoral neck, and T-score +8.5 (Z-score +8.1) and BMD of 2 g/cm<sup>2</sup> for total hip. Markers of bone turnover and calcium metabolism were normal. The ophthalmologic evaluation revealed bilateral papilledema. Head MRI showed mild cerebellar tonsillar herniation through the foramen magnum. Neither pyramidal tract signs nor cerebellar disturbances were present. Genetic analysis detected the A242T mutation in exon 4 of the <i>LRP5</i> gene. To date, 169 patients with Worth's disease have been reported since its first description in 1966, including the present case (Table 1). Neurological involvement and increased serum alkaline phosphatase were present in 33 (19.5%) and 14 (8.2%) cases, respectively. Facial changes and torus palatinus were observed in 96 (56.8%) and 63 (37.4%) cases, respectively. <h3>Conclusion</h3> For the first time, we collected all known case reports of Worth's disease. Neurological involvement is present in one-fifth of the patients, and facial changes are not a consistent finding. Thus, Worth's disease may be asymptomatic and is often incidentally detected in routine radiographs showing generalized osteosclerosis. Our case is the first report of hypo-/anosmia in Worth's disease. <h3>References</h3> [1]Whyte MP et al., <i>Bone</i> vol. 127 (2019): 228-243 [2]Segond et al., Nouv Presse Med 1973; 2(41):2728-32 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.